Angiotensin II is on both a molal and weight basis - the most active vasoconstrictor agent that has been identified. It also acts as a specific tropic hormone controlling the rate of secretion of aldosterone by the adrenal cortex. Therefore, angiotensin II can alter blood pressure both by its effect on vascular reactivity and through its effect on sodium and extracellular fluid volume. Comparative studies of the pharmacologic nature of receptors for angiotensin II on vascular smooth muscle and the glomerulosa cell could be of critical importance in evaluating roles for altered agonist-receptor relationships in disease states. In addition to angiotensin II, the glomerulosa cell is responsive to potassium, ACTH, as well as dietary changes in sodium and potassium. Although in vivo and in vitro studies have reported biochemical events produced by these various regulatory factors, few have related the agonist-receptor interaction with a subsequent biochemical event. The proposed research program, therefore, has the following objectives. The first is to develop a method for purifying adrenal cells both of rat and human origin. Secondly, the pharmacologic nature of the receptors for various regulatory factors of aldosterone biosynthesis will be assessed both by microscopic and biochemical techniques. Thirdly, a comparison of the characteristics of the angiotensin receptors on vascular smooth muscle and the glomerulosa will be performed using structural analogues of angiotensin. Finally, purified cells will be utilized to study aspects of the control of aldosterone biosynthesis where confusion presently exists. Specifically, a series of studies will be designed to examine factors controlling the late pathway in aldosterone biosynthesis, e.g., the conversion of corticosterone to aldosterone. BIBLIOGRAPHIC REFERENCES: Tuck ML, Dluhy RD, Williams GH: Sequential responses of the renin-angiotensin-aldosterone axis to acute postural change: Effect of dietary sodium. J Lab Clin Med 86: 754-763, 1975. Williams GH, Hollenberg NK: 1-Sar, 8-Ala angiotensin II's effect on renal, adrenal and vascular receptors in man: Its usefulness in screening for renal and adrenal diseases. In The Effects of Antihypertensive Therapy, Excerpta Medica Foundation, Amsterdam, 1976. (In press).